2.1. General Calibration Methods for Blood Gas Analysis
Methods of calibrating an oxygen or carbon dioxide sensor for blood gas analyses are known which use wet gases of known composition. Concentrations of oxygen and carbon dioxide are selected to span the range of values anticipated for the clinical measurements. Typically, blood gas analyzers in current use require a two-point calibration method using wet gases of the following composition: 0% oxygen, 10% carbon dioxide, balance nitrogen; and, secondly, 12% oxygen, 5% carbon dioxide and balance nitrogen. Amperometric sensors such as those that measure oxygen concentration are calibrated at "zero" and at the high end of the range. The "zero" calibration is important as it enables any residual background current to be subtracted from the measurement. Potentiometric sensors, such as those for measuring carbon dioxide, are frequently calibrated at a "low" value and a "high" level. The gas mixtures used in the calibration are provided from cylinders equipped with pressure regulators which are attached directly to the analyzer. Such analyzers are commonly bench-top devices.
2.2. Specific Disclosures in the Field
More particularly, U.S. Pat. No. 5,231,030, issued to Deetz et al. Jul. 27, 1993, describes a temperature insensitive calibration system that consists of two phases: (i) an oxygen-containing perfluorocarbon solution; and (ii) a carbon dioxide-containing and solute-containing aqueous phase insoluble in the first phase. The solutes include carbon dioxide-complexing agents, ethylene diamine, bicarbonate, calcium ion, hydroxide ion and others. The multi-phase system is kept under a sealed storage atmosphere "which maintains the desired conditions in equilibrium during the shelf life of the system . . . ". The system disclosed is strictly for controlling the composition of the atmosphere during storage and does not contemplate control over the gas composition after a calibration fluid is released from the package used for storage.
A second Deetz et al. patent, U.S. Pat. No. 5,223,433, issued Jun. 29, 1993. Likewise, this patent discloses a system for controlling the concentration of gases in a sample "medium" independent of a given range of temperature. Control is said to be achieved by including a "reservoir" that is more responsive to changes in temperature than the sample "medium" itself. Thus, the atmosphere, which is common to both sample medium and reservoir, is replenished or depleted in gases almost exclusively from the contents of the reservoir which is made to respond to the changes effected by the change in temperature faster than the sample medium. In this way, the driving force for release or absorption of dissolved gases from the medium to the common atmosphere is adjusted as to diminish changes in the concentration of the dissolved gases in the medium in response to the changes in temperature. (See, in particular, the summary section of the specification.)
U.S. Pat. No. 5,096,669, granted to Lauks et al. Mar. 17, 1992 (the entire disclosure of which is incorporated herein by reference), discloses a disposable device similar to that described in the present invention, including housing, sensor, retaining means, and conduit. The '669 patent also discusses a pouch containing calibrant fluid for calibrating the sensors of the device. The subject matter of the present application is not disclosed, taught, or suggested however.
On the other hand, Enzer et al. in U.S. Pat. No. 4,871,439, which issued Oct. 3, 1989, disclose a disposable self-calibrating electrode package in which one or more containers of reference or calibrating electrolyte solution is present. Preferably, two containers having different compositions are used to allow the system to be calibrated on a two-point basis. (See, col. 4, line 26.) Oxygen and carbon dioxide electrode pairs are also described. U.S. Pat. No. 4,734,184, granted to Burleigh et al. Mar. 29, 1988, contains the same disclosure as the Enzer et al. '439 patent.
U.S. Pat. No. 4,116,336, granted to Sorensen et al. Sep. 26, 1978, describes a calibration packet containing a reference liquid "for the calibration and/or quality control of blood gas analyzers." The reference liquid is enclosed in a flexible, gas-tight container to the exclusion of any gas bubbles. (The total pressure in the liquid is kept below 600 mm Hg to avoid any danger of formation of gas bubbles.) Equilibration of the reference liquid gas composition over the sensor is not disclosed, taught or suggested. Moreover, this patent teaches that the transfer of the reference liquid from the package to the instrument should be done anaerobically. In addition, the '336 patent mentions equilibration only in the context of preparing a reference liquid prior to packaging. (Indeed, the equilibration process is performed overnight at a specified pressure of 600 mm Hg before packaging.)
U.S. Pat. No. 4,062,750 granted to Butler, Dec. 13, 1977, discloses a microfabrication method for the manufacture of thin film polarographic oxygen sensor. The gas permeable layer, which may be established by macro- or microfabrication methods, is, nevertheless intended to enclose both working and reference electrodes completely to form an enclosed structure. Further, at line 43 et seq. the '750 patent describes a recalibration method using room air and the sufficiency of a one point calibration. There is no discussion, however, regarding equilibration of a calibrant fluid.
Also, Hahn, C. E. W., in J. Phys. E: Sci. Instrum. (1980) 13:470-482, outlines a review article in which the principles of blood gas measurement are explored, with an extensive discussion of the historical development of blood gas analyzers. At section 3.2.4., calibration in both air and in liquids is described. Rapid control over the fluid gas composition in the proximity of the sensor itself is not a topic that is even broached. The disclosure also discusses electrodes for the measurement of partial pressure of carbon dioxide and nitrous oxide gases.
Thus, there remains a need for a calibration method that does not rely on control over the dissolved gas composition in a calibrant fluid in storage, which control can be difficult, and ultimately unreliable to maintain over a long period of storage.